The atomic force microscope (AFM) was originally designed as a high-resolution imaging tool for semiconductor scanning applications to allow measurement of atomic level features and forces. The ability to be used in an aqueous environment also allows interaction with biological molecules and even living cells. A unique feature of the AFM is that it is not an optical method, but rather uses a scanning probe that physically contacts the sample to achieve sub-optical resolution. The high-sensitivity force sensor can be used for quantifying the micromechanics involved in pushing, pulling, and manipulating objects from individual molecules to whole cells, providing a unique mapping of the rich mechanobiology landscape. The latest generation of atomic force microscopes allows seamless integration of AFM and confocal microscopy, combining the unique advantages of each method and ushering the AFM out of engineering and biophysics labs and into the hands of cell and molecular biologists who find new applications for this cutting- edge nanotechnology. This shared instrument grant proposes to acquire a state-of-the-art integrated atomic force and real-time confocal microscope as a departmental core facility in the Cardiovascular Research Center. No other such system has ever existed at Mount Sinai, and the current proposal takes advantage of a unique confluence of opportunity and expertise. With an initial cohort of 8 NIH-funded major users, including MDs and PhDs representing 5 departments and 5 NIH institutes, this instrument will significantly impact ongoing research efforts and provide novel ways to achieve the proposed aims. Dr. Costa's new arrival at Mount Sinai will serve as a catalyst to stimulate the imagination and brainstorm ideas while maintaining a firm understanding of the capabilities and limitations of the AFM. The expertise of the PI and the named technician, in consultation with a diverse local management committee, will ensure proper training of users, and maximal and equitable use of the shared instrument. The resulting interactions will open doors for new experiments and interdisciplinary collaborations that were never before possible at Mount Sinai, helping to expand the boundaries of biomedical knowledge and discovery in research at an institution with a top-20 ranking in total NIH investment.